Haem oxygenase (heme,hydrogen-donor:oxygen oxidoreductase (α-methene-oxidizing, hydroxylating)), E.C. 1.14.99.3, converts heme into biliverdin and carbon monoxide, utilizing NADPH as cofactor.

The existence of a third non-catalytic version of haem oxygenase, HO3, has been proposed, although this has been suggested to be a pseudogene [2]. The chemical tin protoporphyrin IX acts as a haem oxygenase inhibitor in rat liver with an IC₅₀ value of 11 nM [1].

* Key recommended reading is highlighted with an asterisk

Abraham NG, Junge JM, Drummond GS. (2016) Translational Significance of Heme Oxygenase in Obesity and Metabolic Syndrome. Trends Pharmacol Sci, 37 (1): 17-36. [PMID:26515032]

Abraham NG, Kappas A. (2008) Pharmacological and clinical aspects of heme oxygenase. Pharmacol Rev, 60 (1): 79-127. [PMID:18323402]

Bilban M, Haschemi A, Wegiel B, Chin BY, Wagner O, Otterbein LE. (2008) Heme oxygenase and carbon monoxide initiate homeostatic signaling. J Mol Med, 86 (3): 267-79. [PMID:18034222]

Bucolo C, Drago F. (2011) Carbon monoxide and the eye: Implications for glaucoma therapy. Pharmacol Ther, 130 (2): 191-201. [PMID:21295073]

* Campbell NK, Fitzgerald HK, Dunne A. (2021) Regulation of inflammation by the antioxidant haem oxygenase 1. Nat Rev Immunol, [Epub ahead of print]. DOI: 10.1038/s41577-020-00491-x [PMID:33514947]

Chan KH, Ng MK, Stocker R. (2011) Haem oxygenase-1 and cardiovascular disease: mechanisms and therapeutic potential. Clin Sci, 120 (12): 493-504. [PMID:21355854]

* Drummond GS, Baum J, Greenberg M, Lewis D, Abraham NG. (2019) HO-1 overexpression and underexpression: Clinical implications. Arch Biochem Biophys, 673: 108073. [PMID:31425676]

George EM, Warrington JP, Spradley FT, Palei AC, Granger JP. (2014) The heme oxygenases: important regulators of pregnancy and preeclampsia. Am J Physiol Regul Integr Comp Physiol, 307 (7): R769-77. [PMID:24898840]

Gozzelino R, Jeney V, Soares MP. (2010) Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol, 50: 323-54. [PMID:20055707]

Khan AA, Quigley JG. (2011) Control of intracellular heme levels: heme transporters and heme oxygenases. Biochim Biophys Acta, 1813 (5): 668-82. [PMID:21238504]

Magierowska K, Brzozowski T, Magierowski M. (2018) Emerging role of carbon monoxide in regulation of cellular pathways and in the maintenance of gastric mucosal integrity. Pharmacol Res, 129: 56-64. [PMID:29360501]

Motterlini R, Foresti R. (2014) Heme oxygenase-1 as a target for drug discovery. Antioxid Redox Signal, 20 (11): 1810-26. [PMID:24180608]

Naito Y, Takagi T, Higashimura Y. (2014) Heme oxygenase-1 and anti-inflammatory M2 macrophages. Arch Biochem Biophys, 564: 83-8. [PMID:25241054]

Otterbein LE, Foresti R, Motterlini R. (2016) Heme Oxygenase-1 and Carbon Monoxide in the Heart: The Balancing Act Between Danger Signaling and Pro-Survival. Circ Res, 118 (12): 1940-1959. [PMID:27283533]

Poulos TL. (2014) Heme enzyme structure and function. Chem Rev, 114 (7): 3919-62. [PMID:24400737]

Rochette L, Cottin Y, Zeller M, Vergely C. (2013) Carbon monoxide: mechanisms of action and potential clinical implications. Pharmacol Ther, 137 (2): 133-52. [PMID:23026155]

Rochette L, Zeller M, Cottin Y, Vergely C. (2018) Redox Functions of Heme Oxygenase-1 and Biliverdin Reductase in Diabetes. Trends Endocrinol Metab, 29 (2): 74-85. [PMID:29249571]

* Ryter SW. (2019) Heme oxygenase-1/carbon monoxide as modulators of autophagy and inflammation. Arch Biochem Biophys, 678: 108186. [PMID:31704095]

Salerno L, Romeo G, Modica MN, Amata E, Sorrenti V, Barbagallo I, Pittalà V. (2017) Heme oxygenase-1: A new druggable target in the management of chronic and acute myeloid leukemia. Eur J Med Chem, 142: 163-178. [PMID:28756878]

* Sasson A, Kristoferson E, Batista R, McClung JA, Abraham NG, Peterson SJ. (2021) The pivotal role of heme Oxygenase-1 in reversing the pathophysiology and systemic complications of NAFLD. Arch Biochem Biophys, 697: 108679. [PMID:33248947]

Sebastián VP, Salazar GA, Coronado-Arrázola I, Schultz BM, Vallejos OP, Berkowitz L, Álvarez-Lobos MM, Riedel CA, Kalergis AM, Bueno SM. (2018) Heme Oxygenase-1 as a Modulator of Intestinal Inflammation Development and Progression. Front Immunol, 9: 1956. [PMID:30258436]

* Szade A, Szade K, Mahdi M, Józkowicz A. (2021) The role of heme oxygenase-1 in hematopoietic system and its microenvironment. Cell Mol Life Sci, [Epub ahead of print]. DOI: 10.1007/s00018-021-03803-z [PMID:33787980]

Tomczyk M, Kraszewska I, Dulak J, Jazwa-Kusior A. (2019) Modulation of the monocyte/macrophage system in heart failure by targeting heme oxygenase-1. Vascul Pharmacol, 112: 79-90. [PMID:30213580]

Vijayan V, Wagener FADTG, Immenschuh S. (2018) The macrophage heme-heme oxygenase-1 system and its role in inflammation. Biochem Pharmacol, 153: 159-167. [PMID:29452096]

Wegiel B, Hanto DW, Otterbein LE. (2013) The social network of carbon monoxide in medicine. Trends Mol Med, 19 (1): 3-11. [PMID:23140858]

1. Drummond GS, Kappas A. (1981) Prevention of neonatal hyperbilirubinemia by tin protoporphyrin IX, a potent competitive inhibitor of heme oxidation. Proc Natl Acad Sci USA, 78 (10): 6466-70. [PMID:6947237]

2. Hayashi S, Omata Y, Sakamoto H, Higashimoto Y, Hara T, Sagara Y, Noguchi M. (2004) Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene. Gene, 336 (2): 241-50. [PMID:15246535]

3. Vlahakis JZ, Kinobe RT, Bowers RJ, Brien JF, Nakatsu K, Szarek WA. (2006) Imidazole-dioxolane compounds as isozyme-selective heme oxygenase inhibitors. J Med Chem, 49 (14): 4437-41. [PMID:16821802]

Subcommittee members: Andreas Papapetropoulos (Co-chairperson) Drug Discovery & Pharmacology Group Department of Pharmaceutical Chemistry Faculty of Pharmacy University of Athens Athens 15771, Greece Csaba Szabo, MD, PhD (Co-chairperson) Department of Anesthesiology The University of Texas Medical Branch at Galveston 601 Harborside Drive Galveston, TX 77555, USA Timothy R. Billiar Department of Surgery University of Pittsburgh Pittsburgh, PA, USA Giuseppe Cirino Department of Experimental Pharmacology University of Naples-Federico II Via Domenico Montesano 49 80131, Naples, Italy David Fulton Vascular Biology Center Georgia Regents University Sanders Building, CB 3940 Augusta, Georgia, USA Roberto Motterlini Director of Research (DR2) Equipe 12 INSERM U955, Faculty of Medicine University of Paris Est Creteil 94010 Creteil France